Cancer is the result of the deregulation of cell proliferation and cell migration. In advanced tumors, cells invade the surrounding tissue and eventually form metastases. This is particularly evident in carcinomas in which epithelial cells have undergone epithelial–mesenchymal transition. Increased cell migration often correlates with a weakening of intercellular interactions. Junctions between neighboring epithelial cells are required to establish and maintain baso-apical polarity, suggesting that not only loss of cell–cell adhesion but also alteration of cell polarity is involved during invasion. Accordingly, perturbation of cell polarity is an important hallmark of advanced invasive tumors. Cell polarity is also essential for cell migration. Indeed, a front-rear polarity axis has first to be generated to allow a cell to migrate. Because cells migrate during invasion, cell polarity is not completely lost. Instead, polarity is modified. From a nonmigrating baso-apically polarized epithelial phenotype, cells acquire a polarized migrating mesenchymal phenotype. The aim of this review is to highlight the molecular relationship between the control of cell polarity and the regulation of cell motility during oncogenesis.